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Biomedical subjects

A Pereira

Publications and source records attributed to A Pereira.

At least 163 records · Page 9Linked to original sources
PubMed1993

The kinesin-like protein KLP61F is essential for mitosis in Drosophila.

We report here that disruption of a recently discovered kinesin-like protein in Drosophila melanogaster, KLP61F, results in a mitotic mutation lethal to the organism. We show that in the absence of KLP61F function, spindle poles fail to separate, resulting in the formation of monopolar mitotic spindles. The resulting phenotype of metaphase arrest with polyploid cells is reminiscent of that seen in the fungal bimC and cut7 mutations, where it has also been shown that spindle pole bodies are not segregated. KLP61F is specifically expressed in proliferating tissues during embryonic and larval development, consistent with a primary role in cell division. The structural and functional homology of the KLP61F, bimC, cut7, and Eg5 kinesin-like proteins demonstrates the existence of a conserved family of kinesin-like molecules important for spindle pole separation and mitotic spindle dynamics.

Amino Acid Sequence↗
PubMed1993

Prothrombin fragment 1 + 2 and thrombin-antithrombin complex measurements indicate continuous and progressive intraoperative thrombin generation in liver transplantation.

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F1 + 2 and TAT progressively rose from preoperative values (1.47 +/- 0.92 nmol/l and 22.41 +/- 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 +/- 2.20 nmol/l, 64.24 +/- 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F1 + 2 6.87 +/- 1.65 nmol/l, TAT 89.32 +/- 7.54 ng/ml), and ATIII levels decreased from 70.61 +/- 12.28 to 57.16 +/- 9.57%. Higher preoperative values of F1 + 2 were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity.

Adolescent↗
PubMed1993

Pneumocystis carinii pneumonia in patients without predisposing illnesses. Acute episode and follow-up of five cases.

Pneumocystis carinii pneumonia (PCP) is described almost exclusively in immunocompromised hosts. This report describes our experience with acute episodes and the follow-up of five patients with PCP who had no known predisposing conditions. The average follow-up period was 3.6 years (range, 2.6 to 4 years). Lymphocyte subpopulations (CD4, CD8, and CD4:CD8), serum immunoglobulins (IgG, IgM, and IgA), and serologic studies for human immunodeficiency virus were carried out on all patients at least twice, both at the beginning and the end of the follow-up. None of the patients presented compatible data with AIDS or any other identifiable risk factors. We conclude that PCP can occur in patients who apparently do not have immunosuppression.

Acute Disease↗
PubMed1993

[Initial iron deposits in idiopathic myelofibrosis. Analysis of 20 patients].

PURPOSE: To analyse the status of iron deposits at diagnosis in patients with idiopathic myelofibrosis (IM). PATIENTS AND METHODS: The study included twenty consecutive patients with IM. Haemoglobin, MCV, serum iron and serum ferritin were determined in each case. Perls stain was used to evaluate iron deposits in bone marrow samples attained by aspiration or biopsy. An attempt was made to correlate the semiquantitative estimation of bone marrow iron with the peripheral blood values connected with iron deposits. RESULTS: Anaemia was present in 15 patients, but in most cases MCV and serum iron were normal. Iron deposits in bone marrow aspirate could be evaluated only in one patient as in the remainders no material was obtained. The semiquantitative estimation of iron in bone marrow biopsy samples showed diminished or absent deposits in 15 cases (75%). In contrast, none of the patients had decreased serum ferritin levels. No correlation was found between bone marrow iron and the peripheral blood values related to iron deposits. CONCLUSION: Most IM patients have decreased bone marrow iron deposits at diagnosis. However, as in chronic myelogenous leukaemia and in essential thrombocytopenia, such finding does not mean a true iron deficiency status.

Bone Marrow↗
PubMed1993

[Transient appearance of anti-erythrocyte autoantibodies during Rh alloimmunization].

Transient appearance of anti-erythrocyte autoantibodies was demonstrated in two women in the first stages of Rh alloimmunization. Any mimicking antibodies, or concurrent autoimmune haemolytic anaemia could be reasonably discarded in both patients. These facts are discussed on the basis of polyclonal activation followed by clonal selection driven by the antigen, as a mechanism of the humoral immune response. Investigation of such cases seems of great interest in subjects with recent alloimmunization in order to assess the incidence of this phenomenon and the antigen systems involved.

Adult↗
PubMed1993

Effect of splenectomy on von Willebrand factor multimeric structure in thrombotic thrombocytopenic purpura refractory to plasma exchange.

Treatment-related changes in plasma von Willebrand factor (vWf) multimers were studied in two patients with thrombotic thrombocytopenic purpura (TTP) undergoing splenectomy because of refractoriness to plasma exchange. In both cases, a decrease in the largest normal vWf multimers was found at presentation. In one case, splenectomy resulted in a long-term remission and was followed by a normal multimeric pattern. In the other case, splenectomy failed to produce a remission and was followed by the appearance of ultralarge multimers, which disappeared--resulting in a normal pattern--when a sustained remission was achieved after vincristine infusion and further plasma exchanges. These results suggest that splenectomy per se has no consistent effect on the vWf multimeric structure in TTP patients, and provide further evidence on the good prognostic value of the achievement of a normal multimeric pattern in these patients.

Adolescent↗
PubMed1993

[Long-term survival in chronic myeloid leukemia: frequency and fundamental characteristics in a series of 100 patients].

PURPOSE: To analyse the frequency and the main clinico-haematologic characteristics of the patients with Ph'-positive chronic myelogenous leukaemia (CML) with long survival. MATERIAL AND METHODS: Of a series of 100 patients with CML diagnosed in the chronic phase and treated in the conventional way at the "Farreras Valentí" School of Haematology between 1969 and 1982, and followed-up for at least 10 years, those surviving more that 8-10 years since the diagnosis were considered eligible for this study. Their clinico-haematological characteristics at diagnosis were compared to those of the remaining patients by means of the Student's t and Mann-Whitney's U tests, plus chi square with the Yates correction. The actuarial survival in the series was assessed according to the Kaplan and Meier method. The Sokal prognostic index was calculated in the longest survivors. RESULTS: The median survival of the series was 45 months (range: 4-171). Ninety-one patients died, 2 are alive in chronic phase and in 7 others the follow-up has been lost in the chronic phase. Eight patients survived more than 10 years and 14 more than eight years. Of these, six were men and eight women, 10 were under 50 years of age, one-half lacked splenomegaly at diagnosis and only 2 had Ph' chromosome mosaicism. According to the Sokal prognostic index, six of these patients were in the low-risk group, four were of intermediate risk, and four others were in the high-risk group. None of them had aplasia due to busulphan during the follow-up. When comparing the initial features of the patients surviving 8-10 years with those of the remainders, only the presence of a lower percentage of blast-cells (p = 0.03) and a lower number of blasts in peripheral blood (p = 0.01) in the former achieved statistically significant difference. CONCLUSIONS: These findings confirm the difficulty in identifying the CML patients with expected long survival at diagnosis. High numbers of cases must be analysed in order to attain definite conclusions in this regard.

Adolescent↗
PubMed1992

[Ferrokinetic studies in the initial evaluation of idiopathic myelofibrosis: results in 18 patients].

BACKGROUND: Since there is no effective treatment for idiopathic myelofibrosis (IM) the determination of possible factors which are involved in the appearance of anemia in this disease may be important from a practical point of view. METHODS: The results of the initial ferrokinetic study analyzed in 18 patients with IM included plasma clearance (T1/2) and globular incorporation (U max) of 59Fe in addition to the uptake of 59Fe in the sacrum, spleen and liver in 16 patients. The clinical-hematologic and histologic data of the different groups of patients identified according to the results of the study were compared. RESULTS: Three ferrokinetic patterns were observed: 1) normal or increased erythropoiesis (8 patient), 2) inefficient erythropoiesis (7 patients), and 3) aplastic pattern (3 patients). The only difference observed between the three groups was the existence of lower levels of Hb and reticulocytes in the subjects with aplastic type pattern. In contrast, although there was an inverse correlation between the medullar and extramedullar uptake of iron (p = 0.018) no relation was observed between the latter and the size of the spleen or liver. CONCLUSIONS: The results obtained in this study indicate that IM behaves heterogeneously from a ferrokinetic point of view.

Adult↗
PubMed1992

Cell lineage-specific expression of modulo, a dose-dependent modifier of variegation in Drosophila.

Variegation in Drosophila is a manifest illustration of the important role played by chromatin structure in gene expression. We have isolated mutants of modulo (mod) and shown that this gene is a dominant suppressor of variegation. Null mutants are recessive lethal with a melanotic tumour phenotype. The mod protein directly binds DNA, which indicates that it may serve to anchor multimeric complexes promoting chromatin compaction and silencing. Using a specific monoclonal antibody we examined by immunocytochemistry the accumulation pattern of mod protein during embryogenesis. The protein is first detected before the blastoderm cellularization in all somatic nuclei, precisely when pericentromeric heterochromatin becomes visible. After the first cell division, mod protein is expressed in lineages of specific embryonic primordia. Based on its dominant phenotype, expression pattern and DNA-binding activity of its product, we propose that mod regulates chromatin structure and activity in specific cell lineages.

Animals↗
PubMed1992

Genetic analysis of a Drosophila microtubule-associated protein.

The 205-kD microtubule-associated protein (205K MAP) is one of the principal MAPs in Drosophila. 205K MAP is similar to the HeLa 210K/MAP4 family of MAPs since it shares the following biochemical properties: it is present in several isoforms, has a molecular mass of approximately 200 kD, and is thermostable. Furthermore, immuno-crossreactivity has been observed between mouse MAP4, HeLa 210K, and Drosophila 205K MAP. Currently, there is little information concerning the biological function of this group of nonmotor MAPs. We have used a classical genetic approach to try to identify the role of the 205K MAP in Drosophila by isolating mutations in the 205K MAP gene. An F2 lethal screen was used to acquire deficiencies of 100EF, the chromosomal location of the 205K MAP gene. Drosophila bearing a homozygous deficiency for the 205K MAP region are fully viable and show no obvious phenotype. A recently developed polymerase chain reaction screen was also used to recover five P-element insertions upstream from the 205K MAP gene. Western blot analysis has shown that these insertions result in hypomorphic mutations of the 205K MAP gene. As was seen with animals that have no 205K MAP, these mutations appear to have no phenotype. These data unambiguously demonstrate that the 205K MAP gene is inessential for development. These results also suggest that there may exist protein(s) with redundant function that can substitute for 205K MAP.

Animals↗
PubMed1991

Thrombin generation and fibrinolysis in the thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT), as well as other coagulation and fibrinolysis parameters, were studied in a series of 13 patients affected by thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). Fragment F1 + 2 was found to be increased in all patients at diagnosis (patients' range, 1.21-19.03 nmol/l; normal limits, 0.28-1.08 nmol/l), and remained also higher than normal after treatment with plasma exchange (patients' range, 1.5-4.01 nmol/l). Even though the analysis of fibrinolysis markers did not show a definite state of hypo or hyperfibrinolysis in the systemic circulation, enhanced circulating D-dimer levels (0.53-12.6 micrograms/ml, normal levels of 0.03-0.29 micrograms/ml) indicated that a certain grade of fibrin lysis was present at previously formed thrombi. Plasma PAI-1 activities either on admission (9.2-38.2 U/ml) and after plasma exchange therapy (2.6-38.6 U/ml) showed a behavior irrespective of t-PA:Ag changes, and post-plasmapheresis values remained high only in patients with fatal neurological outcome. Nevertheless, no correlations between clinical and laboratory data could be established useful for the TTP/HUS prognosis. We conclude that increased thrombin generation occurring in damaged areas is appropriately inhibited by antithrombin III in the systemic circulation, avoiding consumption coagulopathy to develop in uncomplicated patients. In addition, fibrinolysis data suggest that elevated PAI-1 may decisively favor the development of microvascular thrombi.

Antithrombin III↗
PubMed1991

[Paroxysmal cold hemoglobinuria: only in the textbooks?].

Although it was common in the preantibiotic era, paroxysmal cold hemoglobinuria (PCH) is now an exceptional condition. A 34-year-old female with anemia and episodic hemoglobinuria provoked by cold is reported. The laboratory studies suggested intravascular hemolytic anemia, and the Donath-Landsteiner test showed a biphasic IgG hemolysin with anti-P specificity. This finding and the evidence of latent syphilis were diagnostic of PCH. Penicillin therapy suppressed the hemolytic episodes, although the Donath-Landsteiner test is still positive. It is concluded that PCH is still an exisiting disease which should be considered in the differential diagnosis of episodic hemoglobinuria.

Adult↗
PubMed1991

Immune hemolytic anemia and renal failure associated with rifampicin-dependent antibodies with anti-I specificity.

A 50-year-old woman with primary biliary cirrhosis developed immune hemolytic anemia and renal failure while receiving rifampicin for the treatment of refractory pruritus. Serological studies revealed the presence of rifampicin-dependent antibodies of the IgM class that, when tested against a wide panel of erythrocytes, had anti-I specificity. Subsequently, rifampicin was withdrawn and prednisone treatment instituted, this resulting in a rapid resolution of the hemolysis, whereas hemodialysis was required for recovery of the renal function. A role is suggested for the anti-I specificity of the antibodies in the development of renal failure associated with rifampicin therapy.

Anemia, Hemolytic↗
PubMed1991

Evaluation of the transfusion effectiveness of various platelet concentrates by means of an in vitro perfusion technique.

An in vitro perfusion technique was used for the assessment of the effectiveness of platelet concentrates (PCs) administered to patients with bone marrow failure. Denuded rabbit arterial segments mounted in annular chambers were exposed to nonanticoagulated blood drawn directly from the antecubital vein. This perfusion system allows the direct visualization of platelet-subendothelium interactions. The deposition of platelets on exposed subendothelium and the presence of fibrin were evaluated morphometrically. Perfusions were performed before and 10 and 120 minutes after the transfusion of PCs that had been obtained by apheresis and administered immediately after collection (A) or separated by centrifugation of blood units and transfused 24 hours after storage at 22 degrees C (B) or 4 degrees C (C). Bleeding times were also determined systematically. The deposition of platelets on the subendothelium increased significantly (p less than 0.01) 10 minutes after transfusions of A and B PCs, but the presence of fibrin did not differ from pretransfusion values. Two hours after the administration of A or B PCs, the improvement of platelet deposition persisted. By then, the presence of fibrin increased markedly (p less than 0.01). The deposition of platelets was not modified after the transfusion of C PCs, but the presence of fibrin was augmented significantly at both posttransfusion times. Comparisons between bleeding times and morphometric results pointed to a possible role of fibrin formation in contributing to primary hemostasis.

Bleeding Time↗
PubMed1991

Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients.

In a series of 218 subjects diagnosed as having nonleukemic chronic myeloproliferative disorders in a single institution within a 18-year period, 13 instances of acute transformation were registered. They corresponded to 8 out of 70 patients with idiopathic myelofibrosis (IM), 4 out of 91 with polycythemia vera (PV), and 1 out of 57 with essential thrombocythemia (ET). The actuarial probability of developing such a complication at 100 months from diagnosis reached 20.6% in IM, 8.7% in PV, and 4% in ET. Only 1 IM patient whose condition developed into acute leukemia had received prior cytolytic therapy, whereas, in contrast, all PV and ET patients showing this pattern had previously been treated with either 32P or alkylating agents. On the other hand, acute transformation in IM generally had an insidious presentation, contrasting with its abrupt onset in most PV and ET patients. Most acute leukemias (12 out of 13) exhibited a myeloid phenotype. The patients' median survival from diagnosis of the acute transformation was only 3 months, the development of this complication significantly shortening the patients' overall survival.

Actuarial Analysis↗
PubMed1991

Liver dysfunction following splenectomy in idiopathic myelofibrosis: a study of 10 patients.

The hepatic abnormalities that developed after the splenectomy in 10 subjects with idiopathic myelofibrosis were analyzed. In all patients in whom a liver biopsy was performed during the splenectomy, extramedullary hematopoiesis was demonstrated, consisting of dysmorphic megakaryocytes primarily localized in the sinusoids, often accompanied by erythroid precursors. Following splenectomy, a significant increase in both the liver size and serum levels of alkaline phosphatase, bilirubin or gamma-glutamyl transpeptidase was found within 6 months, whereas no such increase was observed in the serum aspartate transaminase and alanine transaminase concentrations. In addition, 2 patients developed acute liver failure leading to death at 3 and 4 weeks from splenectomy, respectively. In contrast with these findings, no hepatic alterations were observed in 10 chronic myeloid leukemia patients who were also submitted to splenectomy.

Adult↗